Immunological and virological factors contributing to the maintenance of persistent virus infections and the pathogenesis of acute infections will be examined. Using the lymphocytic choriomeningitis virus infection of mice as a model both for persistent and acute virus infection, we will analyze the role of defective interfering(DI) virus in the maintenance of persistence and resistance to immune attack mechanisms in vitro and in vivo. The interactions between virus, macrophages, natural killer (NK) cells, and interferon will be studied. Macrophages will be evaluated for their capacity for assimilation and degradation of virus-antibody complexes, for their capacity for anti-viral antibody dependent cell cytotoxicity (ADCC), for their synthesis of interferon, and for their functions under conditions of virus infection in vivo and in vitro. The enhancing and/or suppressing effects of macrophages on NK activity will be analyzed. Similarly, NK cells will be tested for their ability to mediate anti-viral ADCC and to synthesize interferon during acute and persistent LCMV infection. The pathogenesis of LCMV will be examined in NK cell-deficient C57BL/6 beige mice. Correlations will be made between factors (virus infection, interferon, genetic selection) contributing to target cell resistance to NK cell mediated lysis and biochemical alterations in the target cell cytoplasmic membrane.